title: Partial inhibition of insulin secretion results in glucose intolerance but not hyperglucagonemia.
abstract: OBJECTIVE
  We tested the hypotheses that in nondiabetic individuals, partial inhibition of insulin secretion with the ATP-sensitive K(+) channel agonist (opener) diazoxide, compared with placebo, results in higher plasma glucose and higher plasma glucagon concentrations after a mixed meal and after administration of the sulfonylurea glimepiride.
  
  
  METHODS
  Plasma glucose, insulin, C-peptide, and glucagon concentrations were measured every 30 min from -60 through 180 min with random-sequence, double-blind administration of diazoxide (6.0 mg/kg) or placebo at -30 and 1 min, ingestion of a formula mixed meal (Ensure Plus) at 0 min after diazoxide and after placebo and, on a separate occasion, ingestion of glimepiride (4.0 mg) at 0 min (with glucose infused to prevent hypoglycemia) after diazoxide and after placebo in 11 healthy young adults.
  
  
  RESULTS
  With diazoxide administration, insulin (P = 0.0016) and C-peptide (P = 0.0287) concentrations were decreased and glucose concentrations were increased (e.g., 180-min values of 106 ± 4 mg/dL [5.9 ± 0.2 mmol/L] compared with 87 ± 2 mg/dL [4.8 ± 0.1 mmol/L] with placebo; P < 0.0001), but glucagon concentrations were no different after the mixed meal. Similarly, with diazoxide, C-peptide concentrations were decreased (P = 0.0015) and glucose concentrations were increased (P < 0.0001), but glucagon concentrations declined similarly after glimepiride administration.
  
  
  CONCLUSIONS
  Partial inhibition of insulin secretion results in impairment of glucose tolerance after a mixed meal and after glimepiride administration in the absence of a difference in glucagon secretion. They underscore the primary glucoregulatory role of insulin and support the evidence that β-cell secretion is not the only regulator of α-cell glucagon secretion.
authors.affiliation: Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.
authors.forename: Ranjani P
authors.initials: RP
authors.lastname: Ramanathan
authors.forename: Ana María
authors.initials: AM
authors.lastname: Arbeláez
authors.forename: Philip E
authors.initials: PE
authors.lastname: Cryer
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000187:drug effects*; D002096:C-Peptide / Q000097:blood; D003981:Diazoxide / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D005934:Glucagon / Q000097:blood*; D018149:Glucose Intolerance / Q000097:blood / Q000139:chemically induced*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D054086:KATP Channels / Q000819:agonists; D008297:Male; D013453:Sulfonylurea Compounds / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D007004:Hypoglycemic Agents; D007328:Insulin; D054086:KATP Channels; D013453:Sulfonylurea Compounds; C057619:glimepiride; D005934:Glucagon; D003981:Diazoxide